Treating iron deficiency anaemia

ABSTRACT

There are described compounds of formula I, ##STR1## IN WHICH R is allyl, chlorine, bromine, phenyl, or phenyl substituted by one or more halogen or alkyl groups, 
     One of X and Y is a group --CO--, --CHOH-- or --CH 2  -- and the other is an exocyclic carbon-carbon bond linking the ferrocenyl or the R group respectively to the --A-- group, 
     A contains 5, 6 or 7 carbon atoms and is an ethylenically unsaturated (the double bond being connected to the carbon atom which is connected to X), unsubstituted (except by X and Y) cyclic hydrocarbon group; or is a saturated cyclic hydrocarbon group substituted by X and Y and, when X is a group --CO--, optionally substituted on the carbon atom to which Y is attached by an --OH group, and 
     X and Y are attached to adjacent carbon atoms on the A group. There are also described processes for the production of compounds of formula I and haematinic compositions containing them.

This is a division of application Ser. No. 522,591, filed Nov. 11, 1974,now U.S. 3,960,911.

This invention relates to new compounds, a method for their preparationand compositions containing them.

According to our invention we provide compounds of formula I, ##STR2##IN WHICH R is alkyl, chlorine, bromine, phenyl, or phenyl substituted byone or more halogen or alkyl groups,

One of X and Y is a group --CO--, --CHOH-- or --CH₂ -- and the other isan exocyclic carbon-carbon bond linking the ferrocenyl or the R grouprespectively to the --A-- group,

A contains 5, 6 or 7 carbon atoms and is an ethylenically unsaturated(the double bond being connected to the carbon atom which is connectedto X), unsubstituted (except by X and Y), cyclic hydrocarbon group; oris a saturated cyclic hydrocarbon group substituted by X and Y and, whenX is a group --CO--, optionally substituted on the carbon atom to whichY is attached by an --OH group, and

X and Y are attached to adjacent carbon atoms on the A group.

According to our invention we also provide a process for the productionof a compound of formula I, which comprises

A. producing a compound of formula Ia, ##STR3## IN WHICH R is as definedabove, and

L is an unsubstituted cycloalkene group containing 5, 6 or 7 carbonatoms (the double bond being connected to the carbon atom which isdirectly connected to the ferrocenyl radical), by (i) reacting ferrocenewith a compound of formula II,

    rx(CH.sub.2).sub.n COR                                     II

in which

R is as defined above,

n is 4, 5 or 6, and

Rx is --CN, --COOH or an acid halide or anhydride thereof, or (ii)cyclizing and dehydrating a compound of formula III, ##STR4## in which nand R are as defined above,

b. producing a compound of formula Ib, ##STR5## in which R and n are asdefined above, by cyclizing a compound of formula III,

c. producing a compound of formula Ic, ##STR6## in which R and A are asdefined above, and

one of Xa and Ya is a group --CHOH-- or --CH₂ -- and the other is acarbon-carbon bond linking the ferrocenyl or the R group to the A group,Xa and Ya being attached to adjacent carbon atoms in the A group,

by selective reduction of a compound of formula Ia, Ib or Ifrespectively,

d. producing a compound of formula Id, ##STR7## in which A and R are asdefined above, and

one of Xb and Yb is a --C0-- group and the other is a carbon-carbon bondlinking the ferrocenyl or the R group to the A group, Xb and Yb beingattached to adjacent atoms in the A group,

by selective oxidation of a compound of formula Ic in which one of Xaand Ya is a --CHOH-- group,

e. producing a compound of formula Ia in which R is phenyl or phenylsubstituted by one or more halogen or alkyl groups,

by reacting a compound of formula V, ##STR8## in which n and Rx are asdefined above,

with benzene or benzene substituted by up to five halogen or alkylgroups,

or

f. producing a compound of formula If, ##STR9## in which R and n are asdefined above, by dehydrating a compound of formula Ib.

The reaction of processes (a)(i) and (e) may be carried out in a solventwhich is inert under the reaction conditions, for example methylenechloride. The reaction is preferably carried out under Friedel-Craftsreaction conditions, for example in the presence of a Lewis acid such asaluminium chloride. The reaction is preferably carried out at atemperature of from about 0° to 100° C. and preferably from 0° to 45° C.The anhydride may be a symmetrical anhydride or may be a mixedanhydride. Examples of suitable acids from which the mixed anhydride maybe derived are acetic, benzylic and trifluoroacetic acid. When the groupRx is a --CN the product will be an imine which will be hydrolyzed tothe desired compound. We prefer the group Rx to be an acid halide group.Process (a)(i) is preferably not used to produce compounds in which R ischlorine or bromine.

The cyclization and dehydration of process (a)(ii) may be carried out bysubjecting the compound of formula III to acidic conditions, e.g. amixture of sulphuric and acetic acids, or to a Lewis acid in a solventwhich is inert under the reaction conditions, e.g., methylene chloride.The reaction may be carried out at a temperature of from about 0° toabout 100° C., e.g. at about 20° C.

The cyclization of process (b) is preferably carried out under basicconditions and in a suitable, preferably polar, solvent, e.g. dioxane orethanol. The base may conveniently be an alkali metal base, e.g. asodium base. Specifically the process may be carried out using sodiumhydride in dioxane or sodium hydroxide in ethanol. The process mayconveniently be carried out at a temperature of from about 0° to 100°C., and for a time of from about 30 minutes to 24 hours depending on thetemperature used.

The reduction of process (c) may be carried out catalytically, e.g.using palladium on charcoal. The reduction may conveniently be carriedout at a temperature of from 20° to 80° C., e.g. about room temperature(20° C.). The reduction may be carried out at atmospheric pressure, butis preferably carried out at greater than atmospheric pressure.Alternatively the reduction may be carried out chemically using reagentsand reaction conditions known to effect the reduction of --CO-- to--CHOH-- or --CH₂ --; or of --CHOH-- to --CH₂ --. Suitable reducingagents include NaAlH₂ (OCH₂ CH₂ OCH₃)₂. The chemical reduction mayconveniently be carried out at a temperature of from about 0° to 50° C.in a solvent which is inert under the reaction conditions, e.g.methylene chloride or ethanol. When reduction to a --CH₂ -- group isdesired a Clemmensen reduction may be used.

The selective oxidation of process (d) may be carried out in a solventwhich is inert under the reaction conditions, e.g. methylene chloride. Asuitable oxidizing agent is chromium trioxide dipyridine complex. Thereaction may conveniently be carried out at a temperature of from 0° to50° C., and preferably at about room temperature (20° C.).

Process (f) may be carried out under substantially the same conditionsas process (b), but production of the compound of formula I (b) isfavoured by lower reaction temperatures, e.g. below about 20° C., andshorter reaction times.

Compounds of formula II are either known or may be made from knowncompounds using conventional techniques known per se.

The compounds of formula III may be made by carrying out process (a)(i)at a temperature of between about 0° and -25° C. During the productionof the compound of formula III some of the final product of formula Iamay be formed directly. We have found that, in general, use of a lowertemperature and shorter reaction time tends to favour the formation ofthe compound of formula III as opposed to the compound of formula Ia.Compounds of formula III in which R is phenyl or phenyl substituted byup to five halogen or alkyl groups may also be made by reacting acompound of formula V with benzene or benzene substituted by up to fivehalogen or alkyl groups. The reaction may be carried out underconditions similar to those set out above for process (a)(i). Compoundsof formula V may be made from known compounds using conventionaltechniques known per se.

The compounds of formula III have the same utility as the compounds offormula I, but we have found that the compounds of formula I possessconsiderable advantages over those of formula III.

It will be observed that process (a)(ii) may be an intermediate step inprocess (a)(i) and that process (b) may be an intermediate step inprocess (f).

Furthermore both process (b) and process (a)(ii) involve cyclization ofa compound of formula III. In processes (a)(i), (a)(ii) and (b) amixture of compounds of formulae Ia, Ib, III and it may be produced andthe desired compound separated from the mixture using conventionaltechniques, e.g. crystallization from suitable solvents such as ethylacetate; or chromatography on an inert medium such as silica gel usingorganic eluents, such as toluene or petroleum ether/ethyl acetatemixtures. The separation of any such mixtures and the choice of optimumreaction conditions and reagents to produce the greatest yield of anyparticular product is well within the ordinary skill of those working inthis field.

The compounds of formula I are useful because they possesspharmacological activity in animals. In particular, the compounds areuseful as haematinics (as is shown by the rapid correction of irondeficiency anaemia, as determined by following haemoglobin regeneration,in anaemic rats to which the compounds have been administered orally:Lawrence and Bacharach, Evaluation of Drug Activities - Pharmacometrics,Academic Press, New York 1964 page 563) and are useful in the treatmentof iron deficiency in man and other animals, e.g. pigs, horses andcattle. The compounds are particularly useful for the treatment of irondeficiency anaemia in women. A substantial proportion of the doseadministered to rats is transformed into physiologically acceptable ironstores (ferritin) and is retained in organs such as the liver. Thedegree of storage may be determined by measuring the non-haem iron inthe liver by the method of Torrance and Bothwell - South African Journalof Medical Science 1962 Volume 32 page 9. The compounds are particularlyindicated for oral administration.

For the above mentioned use, the dosage administered will, of course,vary depending upon the compound employed, mode of administration andtreatment desired. However, in general, satisfactory results areobtained when administered orally at a daily dosage of from about 1milligram to 250 milligrams active ingredient per kilogram of animalbody weight, preferably given 1 to 3 times a day, or in sustainedrelease form. For man the total daily dosage is in the range of fromabout 50 milligrams to about 2,000 milligrams active ingredient, andunit dosage forms suitable for oral or parenteral administrationcomprise from about 20 to about 2,000 milligrams of the activeingredient.

The compounds according to the invention may be formulated intopharmaceutical compositions with pharmaceutically acceptable adjuvants,carriers or diluents. The nature of the adjuvant, carrier or diluentwill depend in part on the intended mode of administration of thecomposition. Examples of suitable adjuvants, carriers and diluents are:for tablets and dragees - lactose, starch, talc, stearic acid or aneffervescent couple; for capsules - tartaric acid or lactose; for orallyadministered solutions or suspensions and for injectable solutions -water, alcohols, glycerin or vegetable oils; and for suppositories -natural or hardened oils or waxes. The compounds may also be formulatedas a paste, granule, chewable gum or tablet, jelly, drinkable ampule,and/or in combination with a human or animal feedstuff, e.g. bread. Inaddition, the compositions may also include other pharmacologicallyactive components such as Vitamin B12, folic acid, Vitamin C (and/orother vitamins), an analgesic, e.g. aspirin, an anthelmintic or an oralcontraceptive. The composition may also contain suitable preserving,stabilizing and wetting agents, solubilizers and sweetening andcolouring agents and flavourings. If desired, the composition may beformulated in sustained release form or in enteric coated form.Compositions for oral administration are preferred. We prefer to use thecompound of formula I in a solid particulate form having a mass mediandiameter of less than 10, and preferably less than 5 microns.

The compounds of this invention possess pharmacological properties of anorder not demonstrated by similar known compounds.

When R is an alkyl group we prefer it to contain from 1 to 6 carbonatoms, e.g. methyl, ethyl or butyl. When R is phenyl substituted byhalogen or alkyl we prefer mono substitution in the position para orortho to Y. When R is phenyl substituted by halogen we prefer thehalogen to be chlorine or fluorine. When R is phenyl substituted byalkyl we prefer the alkyl to contain 1 to 10, and more preferably 1 to 6carbon atoms. We also prefer the A group to contain 6, or morepreferably 5, carbon atoms. Where the group A is ethylenicallyunsaturated we prefer the double bond to link the two carbon atoms towhich X and Y are attached. We also prefer the group Y to be a --CO--group. Thus as a particularly preferred group we provide compounds offormula Ia in which R is a benzene ring, the benzene ring optionallybeing substituted by a single chlorine atom, or by a single methylgroup, and L is a cyclopentene ring in which the double bond links thecarbon atom attached to the --CO-- group and the carbon atom attached tothe ferrocene nucleus.

Certain of the compounds of formula I exist in optically active form,and we therefore provide the optical isomers themselves and mixtures,including racemic mixtures, thereof. The compounds may be resolved intotheir optical isomers using conventional techniques.

The invention is illustrated, but in no way limited by the followingExamples in which the temperatures are in degrees centigrade.

EXAMPLE 1 1-Benzoyl-2-ferrocenylcyclopentene a. 6-Oxo-6-phenylhexanoylchloride

6-Oxo-6-phenylhexanoic acid (10.3g; 50 mmole), thionyl chloride (25 ml)and dry benzene (150 ml) were heated under reflux for 3 hours. Thereagent and solvent were removed on the rotary evaporator. A further 100ml of benzene was added and the solution again evaporated under reducedpressure (to remove last traces of thionyl chloride). The quantitativelyformed, analytically pure brown solid (mp 53°-56°) was used directly inthe Friedel-Crafts acylation of step (b).

b. 1-Benzoyl-2-ferrocenylcyclopentene

6-Oxo-6-phenylhexanoyl chloride (9.0g; 0.04 mole) and ferrocene (7.44g;0.04 mole) in methylene chloride (150 ml) were stirred at 0° andaluminium chloride (5.34g; 0.04 mole) was added over 40 minutes at 0°.The mixture was stirred at 0° (2 hr), and then at room temperature (90min). More aluminium chloride (4g; 0.03 mole) was added and the reactionmixture was heated under reflux for 90 minutes. Water was added, theorganic layer run off, and the aqueous layer extracted with methylenechloride (100 ml). The combined organic layers were washed with water (3× 200 ml), and dried (sodium sulphate) to yield a brown oil. The portionof this oil which was insoluble in hot cyclohexane was discarded and theremainder (2.7g) was subjected to preparative thin layer chromatographyto yield 2.1g (15%) of pure 1-benzoyl-2-ferrocenylcyclopentene as abrown solid mp 136°-137°.

The procedure described in the preceding paragraph may be replaced bythe following procedure:

Ferrocene (186g; 1 mole) and 6-oxo-6-phenylhexanoyl chloride (224.5g; 1mole) were dissolved in 1,2-dichloroethane (2 1), and aluminium chloride(133.3g; 1 mole) was added with stirring at room temperature over 2 hr.The mixture was left stirring for a further 0.5 hr and then poured intowater (4 1) and the oily solution extracted thoroughly with chloroform(4x). The extracts were washed with water (3x), saturated sodiumbicarbonate (2x) and water, dried (Na₂ SO₄), concentrated to about 500ml and stirred with alumina (400g) for 3 hr. The alumina was removed byfiltration and the filtrate yielded a deep red oil which crystallizedfrom petroleum ether (bp 60°-80°; 800 ml) + chloroform (100 ml). Twofurther crops were obtained on concentrating the mother liquor. Totalyield 155 g. Chromatography of the mother liquors on silica wasperformed. Toluene eluted ferrocene (11g) and toluene/3% ethyl acetateeluted a further pure sample of required compound (39.7g).

The total yield of pure 1-benzoyl-2-ferrocenylcyclopentene was 195g(55%) mp 136°-137°.

EXAMPLE 2 1-Ferrocenoyl-2-phenylcyclopentene

6-Phenyl-6-oxohexanoylferrocene (5.61g; 15 mmole) in sodium drieddioxane (150 ml) was heated under reflux with sodium hydride (0.72g; 30m mole) for 3 hr. The mixture was cooled and treated carefully withwater (200 ml) when a brown solid precipitated, which was filtered offto yield 4.3g (76%) of nearly pure 1-ferrocenoyl-2-phenylcyclopentene.An analytical sample (3.7g; 69%) was obtained by one recrystallizationfrom cyclohexane. mp 163°-164°.

EXAMPLE 3 1-Benzyl-2-ferrocenylcyclopentane and1-(α-Hydroxybenzyl)-2-ferrocenylcyclopentane

1-Benzoyl-2-ferrocenylcyclopentane (7.12g; 0.02 mole) in ethanol (150ml) was submitted to hydrogenation in the presence of palladium oncharcoal (0.8g) at 25 lb/sq inch above atmospheric pressure. After 2days at room temperature, the mixture was filtered (to remove the Pd/C)and the ethanol removed to yield a brown oil, which was chromatographedon silica gel. Toluene eluted pure 1-benzyl-2-ferrocenylcyclopentane(3.5g), mp ca 30°. 'HNMR δ, 7.13 (m 5H); 4.07 (m 9H), 2.5 - 1.0(multiplets 10H)γ max 2950, 1205, 815, 700, and toluene/3% ethylacetateeluted pure 1-(α-Hydroxybenzyl)-2-ferrocenylcyclopentane; a semi solidat room temperature. 'HNMR δ 7.18 (S, 5H); 4.1 (S, 5H); 4.33 → 4.05(multiplets; 1H+4H); 3.2 (doublet of doublets; 1H) 2.35 - 1.2 (m, 8H)γmax 3300 cm⁻.sup. 1.

EXAMPLE 4 1-Benzoyl-2-ferrocenyl-cyclopentane

1-(α-Hydroxybenzyl)-2-ferrocenyl cyclopentane (360 mg; 1 mmole) wasadded to a suspension of chromium trioxide dipyridine complex (1.6g;sixfold excess) in calcium chloride dried methylene chloride (25 ml) atroom temperature with stirring for 1 hr. The suspension was filtered,the organic solution was washed with 2N NaOH (2 × 100 ml), 2N HCl (2 ×100 ml) and water (2 × 100 ml), and dried (Na₂ SO₄) to yield a palebrown oil which crystallized on trituration with petroleum ether.Recrystallization from petroleum ether (bp 40°-60°) gave the desiredproduct as a yellow solid (80 mg; 22%) mp 109°-110° IR:γ max 1670 cm⁻ ¹'HNMR:δ 7.7 and 7.4 (multiplets 5H); 4.0 (s, 5H); 4.1 - 3.9 (m; 4H); 3.5(m, 1H); 2.0 (m; 7H)

EXAMPLE 5 1-Ferrocenyl-2-(4-chlorobenzoyl)cyclopent-1-ene

5-(4-Chlorobenzoyl)pentanoic acid (9.6g; 0.04 mole) in toluene (50 ml)was heated under reflux for 4 hr with thionyl chloride (10 ml; excess).The toluene and excess thionyl chloride were evaporated under vacuum toyield the acid chloride as a pale brown solid which was used directly inthe synthesis of the ferrocene derivative.

5-(4-Chlorobenzoyl)pentanoyl chloride (5.2g; 0.02 mole) in methylenechloride (100 ml) and ferrocene (3.75g; 0.02 mole) were stirred at 0.5°and aluminium chloride (2.7g; 0.02 mole) was added slowly over 0.5 hr.The mixture was stirred at 0.5° for 1.5 hr then water was added. Theorganic layer was separated. The aqueous layer was extracted withmethylene chloride and the combined organic fractions were washed withwater, dried (magnesium sulphate) and evaporated to yield a brown solid.This was recrystallized from petroleum ether (60°-80°) to yield pure5-(4-chlorobenzoyl)pentanoyl ferrocene; 3.23g (40%); mp 103°-106°.

5-(4-Chlorobenzoyl)pentanoyl ferrocene (8.2g; 0.02 mole) and 5% (v/v)concentrated sulphuric acid in glacial acetic acid (200 ml) were stirredat room temperature for 1 hour, the mixture was poured into water andextracted with chloroform (3 × 100 mls.). The combined extracts werewashed with saturated aqueous sodium bicarbonate, and water, dried(magnesium sulphate) and evaporated under vacuum to yield a red-brownoil which crystallized from pentane at 0°-5°. The solid was filtered offto yield pure 1-ferrocenyl-2-(4-chlorobenzoyl)cyclopent-1-ene; 2.5g(35%) mp 121°-123°.

EXAMPLE 6 1-Ferrocenyl-2-(3-methylbenzoyl)cyclopent-1-ene

The title compound was prepared by a similar sequence of reactions tothose described in Example 5 using 5-(3-methylbenzoyl)pentanoylferroceneas starting material.

Yield: 8% mp 110°-3° C.

EXAMPLE 7 3-Benzoyl-2-ferrocenylcyclohexene

7-Oxo-7-phenylheptanoylferrocene (1.94g; 5 mmole) was dissolved in 5% H₂SO₄ /acetic acid (40 ml; excess) at room temperature. The solution wasstirred overnight and then poured into water (400 ml) and extracted withchloroform (3 × 200 ml). The organic layers were extracted with water,saturated aqueous sodium bicarbonate, and water, and dried (Na₂ SO₄) toyield a brown oil. The crude occurrence product was suspended in hotpetroleum ether (bp 40°-60° C.) and filtered. The filtrate was submittedto preparative thin layer chromatography on silica. The main yellow bandwas eluted with petroleum ether/ethyl acetate (10:1) and gave 670 mg(36.2%) of pure 3-benzoyl-2-ferrocenylcyclohexene mp 127°-129° C.EXAMPLE 8

1-Ferrocenoyl-2-hydroxy-2-phenylcyclohexane

6-Benzoylhexanoylferrocene [2.91g; 7.5 mmole] was dissolved in asolution of sodium hydroxide [0.3g; 7.5 mmole] in ethanol [100 ml] andstirred at room temperature for 16 hours.

Filtration and recrystallization from cyclohexanone gave the desiredproduct [1.3g; 47%] mp 172°-173° C.

EXAMPLE 9 1-Chloro-2-ferrocenoylcyclopent-1-ene

Ferrocenoyl valeric acid (3g; 0.01 mole) in toluene (20 ml) was stirredfor 4 hr at 0°-5° with oxalyl chloride (3.8 g; 0.03 mole). The tolueneand excess oxalyl chloride were evaporated off under vacuum to yield apale brown oil which was used directly.

This brown oil (ferrocenoyl valeroyl chloride) assumed to be 0.01 molefrom the above preparation in methylene chloride (100 ml) was stirred at0°-5° and aluminium chloride (1.3g; 0.01 mole) was added. Ice was thenadded and the organic layer was separated. The aqueous layer wasextracted with chloroform. The combined organic fractions were washedwith water, dried (magnesium sulphate) and evaporated to yield a red oilwhich was purified by dry-column chromatography on silica, which hadbeen deactivated to Grade III by the addition of water, using 1:10ethylacetate: petroleum ether as eluent, to yield pure1-chloro-2-ferrocenoylcyclopent-1-ene, 150 mg; mp 102°.

EXAMPLE 10 1-Ferrocenyl-2-(2-fluorobenzoyl)cyclopent-1-ene

5-(2-Fluorobenzoyl)-pentanoylferrocene (16g, 0.04 mole) and 5% v/vconcentrated sulphuric acid in glacial acetic acid (300 ml) were stirredfor 15 minutes at room temperature and were then poured into water. Theaqueous layer was extracted with chloroform. The combined extracts werewashed with water, dried (magnesium sulphate) and evaporated undervacuum. The resulting oil was purified by preparative thin layerchromatography using silica gel, with toluene as eluent, to yield pure b1-ferrocenyl-2-[2-fluorobenzoyl)cyclopent-1-ene as red crystals; 1.2g(8%) mp 90°-92°.

EXAMPLE 11 1-Benzoyl-2-ferrocenylcyclopentene

Ferrocenoylvaleric acid (3.13g; 0.01 mole) in methylene chloride (20 ml)was stirred at 0°-5° for 30 minutes while oxalyl chloride (5 ml) wasadded. After further stirring at room temperature for 30 minutes boththe methylene chloride and excess oxalyl chloride were removed byevaporation at reduced pressure. The resulting light brown oil was useddirectly.

Ferrocenoylvaleryl chloride (prepared as above and assumed to be 0.01mole) was diluted with methylene chloride (10 mls.) and benzene (20mls.) and the solution was cooled to 0°-5°. Aluminum chloride (2.6g;0.02 mole) was then added with stirring over 30 minutes. After furtherstirring at room temperature for 2 hours, ice was added to the reactionmixture. The organic layer was then separated and washed successivelywith water, aqueous sodium bicarbonate solution, and water, before beingdried over sodium sulphate. Evaporation under reduced pressure produceda brown oil from which chromatography on silica gel with toluene/ethylacetate provided a pure sample of the required compound (0.32g; 9%yield) mp 135°-137°.

We claim:
 1. A pharmaceutical composition suitable for use in treatingiron deficiency anaemia comprising, in a unit dose of from 20 to 2000mg., a compound of formulas ##STR10## in which R is alkyl, chlorine,bormine, phenyl, or phenyl substituted by one or more halogen or alkylgroups,X is a group --CO--, --CHOH or --CH₂ --, Y is a group --CO--,--CHOH or --CH₂ --, m is an integer from 1 to 3, and R₁ is hydrogen, oris hydrogen or --OH when X is --CO--as an active ingredient, incombination with a pharmaceutically acceptable adjuvant, diluent orcarrier.
 2. A composition according to claim 1 wherein said compoundis1-ferrocenoyl-2-phenylcyclopentene, 1-benzyl-2-ferrocenylcyclopentane,1-(α-hydroxybenzyl)-2-ferrocenylcyclopentane,1-benzoyl-2-ferrocenyl-cyclopentane,1-ferrocenyl-2-(4-chlorobenzoyl)cyclopent-1-ene,1-ferrocenyl-2-(3-methylbenzoyl)cyclopent-1-ene,3-benzoyl-2-ferrocenylcyclohexene,1-ferrocenoyl-2-hydroxy-2-phenylcyclohexane,1-chloro-2-ferrocenoylcyclopent-1-ene, or1-ferrocenyl-2-(2-fluorobenzoyl)cyclopent-1-ene.
 3. A compositionaccording to claim 1 wherein said compound is1-benzoyl-2-ferrocenylcyclopentene.
 4. A method for treating irondeficiency anaemia in animals, said method comprising administering toan animal having iron deficiency anaemia a therapeutically effectiveamount of a compound of the formulas ##STR11## in which R is alkyl,chlorine, bormine, phenyl, or phenyl substituted by one or more halogenor alkyl groups,X is a group --CO--, --CHOH or --CH₂ --, Y is a group--CO--, --CHOH or --CH₂ --, m is an integer from 1 to 3, and R₁ ishydrogen, or is hydrogen or --OH when X is --CO--.
 5. A method accordingto claim 4 wherein said compound is1-ferrocenoyl-2-phenylcyclopentene,1-benzyl-2-ferrocenylcyclopentane,1-(α-hydroxybenzyl)-2-ferrocenylcyclopentane,1-benzoyl-2-ferrocenyl-cyclopentane,1-ferrocenyl-2-(4-chlorobenzoyl)cyclopent-1-ene,1-ferrocenyl-2-(3-methylbenzoyl)cyclopent-1-ene,3-benzoyl-2-ferrocenylcyclohexene,1-ferrocenoyl-2-hydroxy-2-phenylcyclohexane,1-chloro-2-ferrocenoylcyclopent-1-ene, or1-ferrocenyl-2-(2-fluorobenzoyl)cyclopent-1-ene.
 6. A method accordingto claim 4 wherein said compound is 1-benzoyl-2-ferrocenylcyclopentene.